Femtosecond laser ionization time-of-flight mass spectrometry (fs-LI-TOFMS) is introduced for the three-dimensional elemental analysis of a Nantan meteorite. Spatially resolved multielemental imaging of major and minor compositions in a meteorite are presented with a lateral resolution of 50 μm and a depth resolution of 7 μm. Distinct 3D distributions of siderophile, lithophile, and chalcophile elements are revealed. Co and Ni are highly siderophile (Iron-loving), mainly enriched in the metal phase. Cr, Cu, V, and Mn are enriched in the sulfide for their chalcophile (S-loving) tendency. S, P, and C aggregate together in the analytical volume. Silicate inclusion, containing lithophile elements of Al, Ca, Mg, K, and so on, is embedded within the metal phase for the immiscibility between silicate inclusion and the melted metal phase. These 3D distributions of elements aid the exploration of the formation and evolution of the meteorite. They also reveal the feasibility of fs-LI-TOFMS as a versatile tool for 3D imaging.

A depth profiling technique has been developed and employed for ultra-thin layer analysis using a newly constructed laser desorption and laser postionization time-of-flight mass spectrometer (LD-LPI-TOFMS). This technique achieves the superiority of an extremely low average ablation rate down to ∼0.026 nm in depth per pulse for a series of Ni coated samples with varied thicknesses. Compared to high-cost SIMS apparatus, it offers an alternative strategy for nanometer thin-layer analysis. The integration of the LD-LPI source and TOFMS offers multi-element information on the constituents of each layer and substrate, as well as the trace impurities of sputtering targets. It contributes to comprehensively characterizing nanometer thin layers for the quality evaluation and process control of coatings. Additionally, an underlying capability of this method for the thickness determination of thin-layers was demonstrated. The investigations and results here indicate the potential of LD-LPI-TOFMS as a versatile tool among the available techniques in depth profiling of nanometer thin-layers, filling the gap in ultra-thin layer analysis for laser-based techniques.

The utilization of laser sampling technique in analytical spectrometry has long prevailed as it does not require sample pretreatment, large samples or cause contamination. However, it suffers from a series of defects such as elemental fractionation, matrix effect and shortage of matrix-matched reference materials for most samples of interest. To correct these undesired effects and achieve better analytical performance, it is vital to be conscious of when and how the above deflecting effects occur, to what extent the various parameters involved influence them, and what means can be applied to minimize them. The present review summarizes the research work dealing with elemental fractionation and matrix effects in laser sampling approaches. The review is arranged as follows: Various phenomena of these effects in laser sampling based spectrometry are presented in Section 2; the processes involved are discussed in Section 3; subsequently, the impact of laser parameters and ablation background gas is discussed in Section 4 and 5, respectively; several theoretical studies concerning element-/matrix-specific ablation behavior are briefly considered in Section 6; the means to ultimately minimize elemental fractionation and matrix effect are presented in Section 7; and artificial matrix matched/non-matrix matched analysis approaches are summarized in Section 8.

•The principles of combination systems of scanning probe microscopy (SPM) and mass spectrometry (MS) have been described.•The applications of SPM–MS have been reviewed.•The strengths and the limitations of SPM–MS have been discussed.•Future development trends of SPM–MS have been predicted.The simultaneous acquisition of morphological and chemical information from solid surfaces with a nanoscale lateral resolution is being increasingly considered in modern materials and biological research. Due to their respective advantages, combining scanning probe microscopy (SPM) and mass spectrometry (MS) with field evaporation, thermal desorption, and near-field enhancement is a perfect approach that satisfies the above-outlined research requirements.This review covers the analytical trends of these combined techniques. Relevant research from recent years will be summarized, the principles of the representative techniques highlighted, applications briefly introduced, and potential problems discussed.

•Solid sampling method was developed via pulsed RF discharge at atmospheric pressure.•Crater on oxide sample surface suggests feasibility of sampling nonconductive solid.•Combined with ICPMS, LODs of 10− 8–0− 9 g/g were achieved for most elements.A direct solid sampling technique has been developed based on a pulsed radio-frequency discharge (RFD) in mixture of N2 and Ar environment at atmospheric pressure. With an averaged input power of 65 W, a crater with the diameter of 80 μm and depth of 50 μm can be formed on sample surface after discharge for 1 min, suggesting the feasibility of the pulsed RFD for sampling nonconductive solids. Combined with inductively coupled plasma mass spectrometry (ICPMS), this technique allows to measure elemental composition of solids directly with relative standard deviation (RSD) of ~ 20%. Capability of quantitative analysis was demonstrated by the use of soil standards and artificial standards. Good calibration linearity and limits of detection (LODs) in range of 10− 8–10− 9 g/g were achieved for most elements.

Pulsed microdischarge employed as source for direct solid analysis was investigated in N2 environment at atmospheric pressure. Compared with direct current (DC) microdischarge, it exhibits advantages with respect to the ablation and emission of the sample. Comprehensive evidence, including voltage–current relationship, current density (j), and electron density (ne), suggests that pulsed microdischarge is in the arc regime while DC microdischarge belongs to glow. Capability in ablating metal samples demonstrates that pulsed microdischarge is a viable option for direct solid sampling because of the enhanced instantaneous energy. Using optical spectrometer, only common emission lines of N2 can be acquired in DC mode, whereas primary atomic and ionic lines of the sample are obtained in the case of pulsed mode. Calculations show a significant difference in N2 vibrational temperatures between DC and pulsed microdischarge. Combined with inductively coupled plasma mass spectrometry (ICPMS), pulsed microdischarge exhibits much better performances in calibration linearity and limits of detection (LOD) than those of DC discharge in direct analysis of samples of different matrices. To improve transmission efficiency, a mixture of Ar and N2 was employed as discharge gas as well as carrier gas in follow-up experiments, facilitating that LODs of most elements reached ng/g.

A graphical abstract is available for this content

This review focuses on the developments of atomic spectrometry (AS) in China since the founding of the People's Republic in 1949. The content covers atomic emission spectrometry (AES), atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS), and elemental mass spectrometry (ElemMS), together with related hyphenated techniques and sample introduction techniques. The first section covers the topic of the development history of atomic spectrometry in China. The intriguing developments in instrumentation, technique and methodology are listed with novel excitation/atomization sources highlighted. The second section deals with the aspects of hyphenated techniques, including on-line sample pre-treatment method for separation/preconcentration, and the chromatography-atomic spectrometry hyphenated techniques. The third section briefly demonstrates sample introduction techniques, which are vital for the enhancement of detectability. All these works indicate that the advancement of AS in China contributes to the development of methodology, application and instrumentation in the AS world.

A novel strategy for the generation of metal–peptide complexes in the gas phase is proposed, which is of great value for probing the interactions of “naked” metal ions with peptides. “Naked” metal ions are generated from the metal target by laser ionization (LI) in open air, whereas gas-phase peptide ions are electrosprayed separately, facilitating the formation of gas-phase metal–peptide complexes. Compared to the conventional electrospray ionization (ESI) method, more control is offered for generating complexes, avoiding signal suppression and dilution effects induced by electrospraying solutions composed of metal salts and peptides. Higher stabilities of metal–peptide complexes can be obtained by a direct gas-phase reaction of peptides with “naked” metal ions devoid of counter-ions and surrounding solvent due to stronger noncovalent interactions, such as coulomb interactions and charge–dipole interactions. This approach leads a knowledge of the intrinsic properties of complexes and provides accurate gas-phase results in closer proximity to theoretical calculations irrespective of the solvent effect. The influence of the number and position of basic residues in peptides on the binding site of metal ions and CID fragmentation patterns of complexes is explored and discussed. Plausible mechanisms responsible for fragments remote from the initial binding sites of metal ions are proposed. Additionally, the diffusion model is introduced to expound on the high reaction yield of metal–peptide complexes and distribution evolution of metal ions, verified by both the calculated and experimental results.

•Depth profile technique has been developed for ultrathin layer analysis.•Pulsed micro-discharge was used for solid surface sampling.•Discharge can be controlled by voltage, pulse width, and frequency.•Ablation rate can be controlled, 0.6 nm in depth per pulse was achieved.•Thickness determination using the calibration curve was demonstrated.A depth profile technique has been developed for ultrathin layer analysis by combining a pulsed micro-discharge device with inductively coupled plasma mass spectrometry (ICPMS). With a tungsten needle as the anode and the sample as the cathode, a local micro-plasma was formed in the 50 μm discharge gap, which contributed to the ablation of the sample. We analyzed a series of Ni coating samples with thicknesses of 5, 10, 15, and 20 nm in this study. Although the micro-discharge was shown to be an arc, pulsed mode operation provided an extra control over the power output and the discharge time that enabled precision ablation of submillimeter in lateral scale and 0.6 nm in depth per pulse. A further attempt was made to demonstrate the ability in thickness determination using the calibration curve for layers of different thicknesses. Our results show that the pulsed micro-discharge could directly ablate a solid sample under ambient conditions and that it is an effective low-cost method for depth profiling of nanometer thin layers.

•Matrix effect is one of the obstacles in direct solid analysis.•RSCs combined with physical properties were analyzed by chemometrics tool.•S-plot reveals thermal property playing vital role in matrix effect in ns-laser ablation.•Theoretical model was built to simulate RSCs.•Model prediction of RSCs shows a relatively close agreement with experimental result.Matrix effect is one of the shortcomings of direct solid analysis which makes the quantitative analysis a great challenge. All of the physical properties of solid and laser parameters could make contributions to the matrix effect. For better understanding and controlling laser ablation process, it is of great importance to investigate how and to what extent these factors would affect matrix effect, through simulation and chemometrics works.In this study, twenty-three solid standards of six types of metal matrices were analyzed, including aluminum, copper, iron, nickel, tungsten and zinc. The influence of laser pulse duration was investigated by applying nanosecond (ns) and femtosecond (fs) lasers to a buffer-gas-assisted ionization source coupled with an orthogonal time-of-flight mass spectrometer. After relative sensitivity coefficients (RSCs) of each element in different matrices were calculated, they were combined with the physical property values of the matrices to form a dataset which was analyzed by the chemometrics tool of orthogonal partial least-squares (OPLSs). The S-plot result reveals that thermal properties of solid play vital roles in the matrix effect induced by ns-laser ablation, while fs-laser could significantly reduce the thermal effect. Additionally, a theoretical model was figured out to simulate the RSCs by combining the laser–solid interaction process and plasma expansion process. The model prediction shows a relatively close agreement with experimental result, revealing that the model could reasonably explain the process of matrix effect.

Comprehensive analysis of organic compounds is crucial yet challenging considering that information on elements, fragments, and molecules is unavailable simultaneously by current analytical techniques. Additionally, many compounds are insoluble or only dissolve in toxic solvents. A solvent- and matrix-free strategy has been developed which allows the organic compound analyzed in its original form. It utilizes thermal diffusion desorption with the solid analyte irradiated with high energy laser. It is capable of providing explicit elemental, fragmental, and molecular information simultaneously for a variety of organic compounds. Thermal diffusion desorption has many advantages compared to the electrospray and MALDI techniques. The protons that form the protonated molecular ions originate from the analyte itself. All the elements and fragments are also derived from the analyte itself, which provides abundant information and expedites the identification of organic compounds.

High-irradiance laser ionization time-of-flight mass spectrometry (LI-TOFMS), an established technique for elemental determination, has been applied for the analysis of metalloporphyrins. Many porphyrins and their metal complexes, being organometallic compounds, are hard to dissolve in general organic solvents, hampering the wider application of traditional mass spectrometric techniques. With LI-TOFMS, an environmentally friendly analytical strategy has been demonstrated, which is capable of matrix- and solvent-free analysis of metalloporphyrins, with advantages including direct solid sampling, ease of implementation, and avoidance of sample pre-treatment. Moreover, information about elemental composition, fragments, and intact molecules can be obtained simultaneously using LI-TOFMS, hence expediting the identification of metalloporphyrins. A comparative study of LI-, laser desorption ionization (LDI-), matrix-assisted laser desorption ionization (MALDI-) and electrospray ionization (ESI-) mass spectrometry (MS) has also been conducted.

•Dominating mechanisms concerning ion emission kinetics are briefed.•Diagnostic methods for ion kinetic energy distributions are classified.•Features of kinetic energy distributions and angular distributions are reviewed.•Dependences on laser parameter, ambient condition, and target property are summarized.Studies of ion emissions from laser-induced plasmas (LIPs) provide insights into the hydrodynamic expansion of the plume. Investigations of the kinetic energy distributions (KEDs) of ionized species for various experimental conditions are vital for a fundamental understanding of the formation and expansion dynamics of plasma. This knowledge, in turn, leads to promising improvements in LIP-based technological applications.This article aims to review some of the dominating mechanisms concerning ion emission kinetics during laser-surface interactions from a basic point of view. The diagnostic methods for ion KEDs are roughly classified. Interesting features of ion KEDs and their angular distributions, as well as the dependence on laser beam properties, ambient surroundings, and target properties, are summarized.

•Fundamental theories and calculation methods of LIP temperature are reviewed.•Influences of various factors on LIP temperature are discussed.•Various explanations are given to interpret the temperature behaviors.It is of great importance to explore the evolution of laser-induced plasma (LIP) properties, especially plasma temperature, with regard to variations of experiment conditions in both theoretical study and routine applications. By investigating the influence of various factors on plasma temperature, one can gain knowledge about the processes in plasma and adjust experimental conditions to obtain optimum analytical performance.Herein the fundamental theories and calculation methods of LIP temperature via spectroscopic approaches are briefly reviewed. Its temporal and spatial evolutions together with several influencing factors are discussed, such as laser parameters, ambient surrounding, and physical & chemical properties of the sample. The results summarized exhibit the general trend that LIP temperature increases with increasing laser wavelength, pulse width, laser energy, background gas pressure, and sample hardness. On the other hand, it decreases with time elapsing and distance from sample surface. Moreover, plasma temperature generated in argon surrounding is higher than that in other gas species, and the rank of temperature values generated from different samples exhibits a general tendency of Cu > Fe > Ni ≈ Al ≈ glass ≈ rock. Additionally, LIP temperature tends to increase as lens focal point approaches sample surface, and the plasma confinement effect in sample cavity is significant in altering plasma temperature. Various explanations are given to interpret these temperature behaviors.

Matrix effect is unavoidable in direct solid analysis, which usually is a leading cause of the nonstoichiometric effect in quantitative analysis. In this research, experiments were carried out to study the overall characteristics of atomization and ionization in laser–solid interaction. Both nanosecond (ns) and femtosecond (fs) lasers were applied in a buffer-gas-assisted ionization source coupled with an orthogonal time-of-flight mass spectrometer. Twenty-nine solid standards of ten different matrices, including six metals and four dielectrics, were analyzed. The results indicate that the fs-laser mode offers more stable relative sensitivity coefficients (RSCs) with irradiance higher than 7 × 1013 W·cm–2, which could be more reliable in the determination of element composition of solids. The matrix effect is reduced by half when the fs-laser is employed, owing to the fact that the fs-laser ablation and ionization (fs-LAI) incurs an almost heat-free ablation process and creates a dense plasma for the stable ionization.

In modern bioanalytics, elemental analysis of single cells is important yet challenging due to the complicated biological matrices and elemental contents. We have developed the high irradiance femtosecond laser ionization orthogonal time-of-flight mass spectrometry (fs-LI-O-TOFMS) to determine the elemental composition of individual cells. The sample preparation procedure is simple and fast through heating and drying the cells. Under typical operating conditions, elements above femtogram levels in a single cell can be clearly observed in the spectrum with reasonable isotope ratios. Some of the nonmetallic elements that are difficult to measure by ICPMS, such as P, S, and Cl, can be easily determined by fs-LI-O-TOFMS. Replicate analyses show that signal variations are 15–35% for metallic elements and 25–50% for nonmetallic elements. The results demonstrate that fs-LI-O-TOFMS is a simple, rapid, and practical tool for the elemental determination of single cells.

Ions in Matrix-Assisted Laser Desorption/Ionization (MALDI) are predominantly singly charged for small analyte molecules. With the estimated high number density and low temperature of electrons, the three-body recombination mechanism is attractive and should be considered as an important cause for the charge reduction in the plume. Theoretical calculations indicate that the rate coefficient of the three-body recombination is about 50 times higher than that of the two-body recombination if the analyte molecule has insufficient degrees of freedom. Experimental results show that, for small analyte molecules, the ratio of AH22+/AH+ is close to the theoretical 5% value from the three-body recombination modeling and this ratio declines with the increasing electron and matrix molecule number density caused by greater laser irradiance. The ratio of [A + 2]+/[A + 1]+ is higher than the theoretical isotopic value, and the excess [A + 2]+ could exclusively result from the three-body recombination collisions. Further evidence demonstrates that [A + 2]+/[A + 1]+ increases with electron number density, which is in correspondence with the model. All of these theoretical and experimental results indicate that three-body recombination is an essential charge reduction mechanism for small molecules in the MALDI plume.

High irradiance femtosecond laser ionization orthogonal time-of-flight mass spectrometry (fs-LI-O-TOFMS) has been applied for the depth profile analysis of multilayer samples. Elements in each layer can be determined with respect to the depth of solid sample surfaces. A nanosecond laser was also applied in parallel for comparison. The analytical performances as well as crater formation mechanisms of femtosecond and nanosecond laser ablation and ionization were compared. Superiorities of the depth resolution and trace elemental detection were observed in the femtosecond laser mode. fs-LI-O-TOFMS is capable of presenting the complete and explicit spectrum for each laser shot, performing depth profiling of coated layers with various thicknesses (tens of nanometers to tens of micrometers), providing multi-elemental information, and examining samples with conductive and nonconductive substrates.

The clinical exploration of urinary metabonomic analysis on discriminating between the top-two-incidence urological cancers, bladder and kidney cancers (BC and KC), is still virgin land. In this study, we discovered and evaluated the clinical utility of holistic metabonomic profiling and current single biomarker methods, and ultimately suggested a potential screening test for BC and KC. Urine metabonomic profiling for 19 BC patients, 25 KC patients, and 24 healthy controls was carried out using an LC–MS based platform, which utilized both reversed phase chromatography and hydrophilic interaction chromatography. The holistic method that refers to orthogonal partial least-squares-discriminant analysis based on all qualified profile data, successfully classified BC, KC and healthy control groups, showing 100 % sensitivity and specificity. Taurine, hippuric acid, phenylacetylglutamine and carnitine species contributed most to the BC and KC discrimination. The predictive power of each above metabolite is evaluated using receiver operator characteristic technique. Hippuric acid was found 10-fold decrease in concentration relative healthy controls, and performed the best as a biomarker for BC diagnosis, with its sensitivity and specificity of 78.9 and 86.5 %, respectively. Carnitine C10:3 was found 1.5-fold decrease, and reached 84.0 % of sensitivity and 60.5 % of specificity for KC diagnosis. In view of both sensitivity and specificity, the holistic method is more accurate for detecting BC and KC, than current single metabonomic biomarker methods, and it could be advocated as a prescreen to other forms of more invasive or uncomfortable screening. Moreover, this approach also demonstrates attractive performance in diagnosis of early stage (ES) BC and KC patients.

•LI-O-TOFMS was applied for the elemental mapping of polymetallic nodules.•The contents and distributions of elements of a polymetallic nodule were revealed.•2 groups of elements, Mn–Ni–Cu–Fe and Co–Si–Al, show inter-element relationships.•Physico-chemical conditions during the nodule formation could be reflected.•LI-O-TOFMS is proven to be a powerful tool for the analysis of polymetallic nodules.A newly developed two-dimensional mapping high irradiance laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS) has been applied for the elemental mapping of polymetallic nodules. Two polymetallic nodule standards were used to demonstrate the efficacy of LI-O-TOFMS for the standardless semiquantitative analysis and the spatial distribution of elements in a deep-sea Pacific polymetallic nodule was mapped. It was found that the two groups of elements, Mn–Ni–Cu–Fe and Co–Si–Al, show clear element-dependent spatial relationships. It is hypothesized that these spatial distributions reflect the environmental and physico-chemical conditions during the nodule formation. LI-O-TOFMS is shown to be a powerful tool in elemental analysis of polymetallic nodules, with the detection limits down to 10− 7 g/g and a dynamic range of 7 orders of magnitude. Based on the images acquired, the contents of elements and their relationships can be revealed visually.

An elemental analysis method was established to monitor the element levels in serum samples of 38 healthy controls and 38 stone patients. Based on the optimized platform combined with multivariate analysis, satisfactory results can be obtained for urinary lithiasis diagnosis with the concentrations of 9 elements, in which Ba, Ga, Sb, and Na are the top 4 elements of statistical significance. The patients could be subdivided into calcareous and non-calcareous stone patients by metallomic profiling; and it is found that Se plays the major role in this classification. This study indicates that serum elementary analysis gives an insight into the possibility of diagnosis of urinary lithiasis, subsequently it may allow estimation of the content subtype of stones. By means of this simple method of elemental profiling in serum, it might allow early prognosis and treatment guide to urinary lithiasis.

The characteristics of laser ionization in low pressure background gas have been investigated through the measurement of temporal and kinetic energy distributions of Al+, Mn+, Nb+, In+, Ta+, and Bi+ produced from a disk comprised of these metallic elements. A Q-switched Nd:YAG laser was utilized with a laser beam at 532 nm of wavelength and 1.0 × 1010 W/cm2 of laser irradiance. The kinetic energy was found to be the same for all ablated species at the given pressure, regardless of the atomic mass. The plume propagation translates from a free expansion at 0.5 Pa to a collisional and shockwave-like hydrodynamic expansion at 50 Pa. A plume splitting exists at 500–1500 Pa where only the fast component can be observed with a grounded nozzle voltage. As the nozzle voltage grows up, the thermalized component with increased kinetic energy is found depending on the nozzle voltage.Highlights► We have measured kinetic energy distributions of different elements. ► Two approaches were used for measurement: temporal profile and deflecting voltage. ► Kinetic energy distributions are the same for different species, independent of mass. ► Kinetic energy loss of ions is much smaller than the theoretical value. ► Kinetic energy of the slow component increases proportionally with nozzle voltage.

A novel method for obtaining elemental, fragmental, and molecular information of organometallic compounds has been developed using high irradiance laser induced time-of-flight mass spectrometry (LI-TOFMS) with a buffer-gas-assisted ion source. This technique permits direct and matrix-free analysis of solid analyte with minimal sample preparation. In addition, it shows special advantages in integrated acquisition of elemental, fragmental, and molecular information from a single target, on the basis of which identification of organometallic complexes is simplified and expedited.

A LC−MS based method, which utilizes both reversed-performance (RP) chromatography and hydrophilic interaction chromatography (HILIC) separations, has been carried out in conjunction with multivariate data analysis to discriminate the global serum profiles of renal cell carcinoma (RCC) patients and healthy controls. The HILIC was found necessary for a comprehensive serum metabonomic profiling as well as RP separation. The feasibility of using serum metabonomics for the diagnosis and staging of RCC has been evaluated. One-hundred percent sensitivity in detection has been achieved, and a satisfactory clustering between the early stage and advanced-stage patients is observed. The results suggest that the combination of LC−MS analysis with multivariate statistical analysis can be used for RCC diagnosis and has potential in the staging of RCC. The MS/MS experiments have been carried out to identify the biomarker patterns that made great contribution to the discrimination. As a result, 30 potential biomarkers for RCC are identified. It is possible that the current biomarker patterns are not unique to RCC but just the result of any malignancy disease. To further elucidate the pathophysiology of RCC, related metabolic pathways have been studied. RCC is found to be closely related to disturbed phospholipid catabolism, sphingolipid metabolism, phenylalanine metabolism, tryptophan metabolism, fatty acid beta-oxidation, cholesterol metabolism, and arachidonic acid metabolism.

Characteristics of laser ionization in vacuum and low pressure background gas (He) have been investigated through the measurement of kinetic energy and spatial distributions of copper and tungsten ions. A Q-switched Nd:YAG laser with 532 nm wavelength was utilized and the laser irradiance was fixed at 9 × 109 W cm−2. A plume splitting was observed in the low pressure regime investigated (from 100 Pa to 2000 Pa). The plume propagation translates from a free expansion in vacuum to shockwave-like expansion at relative low pressure and finally diffusion into background gas at relative high pressure environment. A measurement of ion spatial distribution in the ion source has also been carried out for characterizing ions at different pressures and the behaviors of doubly charged, singly charged, and polyatomic ions to reveal the effect of plume–background gas interaction.

Peptidomics plays an important role in clinical proteomics and disease-associated biomarker discovery. It has exhibited mounting potential in early noninvasive diagnosis, prognosis, and treatment evaluation of diseases. This article presents an introduction of peptidomics, the entire peptidomic workflows for serum and urine samples, and a brief overview of recent works in this area. The review is designed to enable researchers to find the most suited strategy for their peptidome studies.

The simultaneous determination of nonmetallic elements in solid samples is difficult owing to their discrepant physical and chemical properties. We developed a high-irradiance laser ionization orthogonal time-of-flight mass spectrometry (LI-O-TOFMS) system and applied it for the determination of nonmetallic elements in solids. Helium was used as the buffer gas at 250 Pa in the source chamber; the laser irradiance was about 7 × 1010 W/cm2. A series of artificial standards containing B, C, N, O, F, Si, P, S, Cl, As, Br, Se, I, and Te were used. Explicit spectra were obtained with only a little interference from gas species and doubly charged matrix ions. Standardless semiquantitative analysis could be accomplished with a novel sampling methodology to obtain near-uniform sensitivity coefficients for different elements. Limits of detection (LOD) at microgram per gram level and a dynamic range of 6 orders of magnitude were achieved for most nonmetallic elements.

The capabilities of two-dimensional separation using a high irradiance laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS) were demonstrated in this paper. Ions were separated via their initial kinetic energy in one dimension and their mass-to-charge ratios in the other dimension. Investigation of the transient ion profiles after laser pulses revealed that the separation of analyte ions from multiply charged ions and gas species ions was achieved. Comparison of mass spectra in the normal accumulation mode and in the two-dimensional separation mode indicated that the relative sensitivity coefficients are stable and close to their true values in the two-dimensional separation mode, especially for trace elements that are prone to interference.

Serum samples from kidney cancer patients and healthy controls were analyzed by both direct infusion mass spectrometry (DIMS) and liquid chromatography-mass spectrometry (LC-MS) with a high resolution ESI-Q-TOFMS. The classification and biomarker discovery capacities of the two methods were compared, and MS/MS experiments were carried out to identify potential biomarkers. DIMS had comparable classification and prediction capabilities to LC-MS but consumed only ∼5% of the analysis time. With regard to biomarker discovery, twenty-three variables were found as potential biomarkers by DIMS, and 48 variables were obtained by LC-MS. DIMS is recommended to be a fast diagnostic method for kidney cancer, while LC-MS is necessary when comprehensive screening of biomarkers is required.

A laser ionization orthogonal time-of-flight mass spectrometer with a low-pressure source and high laser irradiance was used to analyze 27 solid samples with 9 different matrices, including aluminium, soil, copper sulfide, zinc sulfide, iron, nickel, copper, zinc, and tungsten. The influence of laser energy on non-stoichiometric effects, such as matrix effects and elemental fractionation, has been investigated. The results indicate that matrix effects can be alleviated to a great extent at high laser irradiance. Additionally, with the irradiance of 1010–1011 W cm−2, most elements presented relatively stable relative sensitivity coefficients (RSC), while W, Pb, and Bi demonstrated unusual characteristics that their RSCs increased along with increasing laser energy.

A novel method has been developed that allows the direct speciation analysis of iron oxides based on a modified laser ionization orthogonal time-of-flight mass spectrometer. Time resolved mass spectra were acquired for the investigation of elemental ions and oxide ions generated by a laser ionization source. Speciation methodologies, including the identification of characteristic ions and the use of ion abundance ratios were evaluated for the differentiation of the oxides. The influence of operating parameters on the distribution of cluster ions was investigated, and their mechanism of formation discussed.

An enclosed device surrounding the argon inductively coupled plasma torch was fabricated to exclude air entrainment and attenuate background interferences. Helium was introduced into the enclosure, and ambient helium plasma was formed stably. Under cold plasma condition, we found that the spectral background decreased about 1 order of magnitude averagely compared with that in typical operation condition. For laser ablation with a Nd:YAG laser, the limits of detection of 28Si, 29Si, 31P, and 32S in an iron matrix were improved significantly; the linearity of their calibration curves was greatly improved as well compared with standard mode and cool mode ICP-MS with no ambient helium. The result indicates that polyatomic interferences from nitrogen, oxygen, hydrogen, carbon, etc. were effectively reduced in helium ambient ICP-MS.

Mass spectrometry using a laser ionization source has played a significant role in elemental analysis. Three types of techniques are widely used: high irradiance laser ionization mass spectrometry is capable of rapid determination of elements in solids; single particle mass spectrometry is a powerful tool for single particle characterization; and resonance ionization mass spectrometry is applied for isotope ratio measurements with high sensitivity and selectivity. In this review, the main features of the laser ablation process and plasma characterization by mass spectrometry are summarized. Applications of these three techniques for elemental analysis are discussed.

Serum and urine samples from patients with type 2 diabetes mellitus and control samples were analyzed by UPLC-TOF-MS; fast and slow separation gradients were compared using both positive and negative ionization modes. The resulting data were analyzed using partial least squares discriminant analysis (PLS-DA), and models were developed to differentiate between patient and control samples. The models were evaluated using external test sets to classify their predictive ability. Under both fast and slow gradient conditions, the PLS-DA models generated using serum samples were more robust than those generated using urine samples, and the positive ionization mode produced better differentiation and higher classification rates than negative ionization mode. In addition, fast gradient conditions were found to have a comparable ability for differentiation to slow gradient conditions.

A compact high-irradiance laser ionization time-of-flight mass spectrometry system has been developed for the multielemental analysis of solids. Helium was introduced into the ion source as a buffer gas to cool high kinetic energy ions and suppress the interference of multicharged ions. A special pulse train repelling mode was used to achieve explicit spectra. Two quantitative methods are described for the laser ionization mass spectrometry in this paper. The first of these is the routine calibration curve quantitation, in which various matrix-matched standards are required; the second method, which is based on the uniform correlation between the signal and elemental concentration of different samples, is more convenient and covers a typical dynamic range of 6 orders. All the investigations and results indicate satisfactory performance of the newly developed instrument and its applicability for simultaneous multielemental analysis of solid samples.

A newly developed high irradiance laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS) was employed for the elemental analysis of residues, which were prepared by evaporating mixed salt solutions. The residues were first characterized in terms of shape and elemental distribution. In TOFMS detection, all of the metal elements in the residue can be observed in the spectra. Relative sensitivity coefficients for different elements were within 1 order of magnitude, which meets semiquantitative analysis criteria. By calculating the individual masses from the ablated area due to a single laser shot, the absolute detection limit reached 7 × 10−15 g for most metal elements. The results indicate that LI-O-TOFMS is capable of performing ultratrace elemental qualification and quantification, with an absolute limit of detection and an absolute limit of quantitation at the femtogram level.

Ultra performance liquid chromatography (UPLC) coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry has showed great potential in diabetes research. In this paper, a UPLC–oaTOF-MS system was employed to distinguish the global serum profiles of 8 diabetic nephropathy (DN) patients, 33 type 2 diabetes mellitus (T2DM) patients and 25 healthy volunteers, and tried to find potential biomarkers. The UPLC system produced information-rich chromatograms with typical measured peak widths of 4 s, generating peak capacities of 225 in 15 min. Furthermore, principal component analysis (PCA) was used for group differentiation and marker selection. As shown in the scores plot, the distinct clustering between the patients and controls was observed, and DN and T2DM patients were also separated into two individual groups. Several compounds were tentatively identified based on accurate mass, isotopic pattern and MS/MS information. In addition, significant changes in the serum level of leucine, dihydrosphingosine and phytoshpingosine were noted, indicating the perturbations of amino acid metabolism and phospholipid metabolism in diabetic diseases, which having implications in clinical diagnosis and treatment.

A method has been developed that allows the direct measurement of the elemental composition of geological samples based on a newly developed laser plasma time-of-flight mass spectrometer with a collisional cooling system. This technique has the merits of small sample consumption and rapid elemental analysis. Four geological reference materials were used in the experiment. The system has shown a satisfactory resolving power with few interferences in the spectra. The limits of detection were about 10−6–10−7 g g−1 for most of the metal elements. The relative sensitivity coefficients (RSCs) of the elements with mass heavier than 30 amu could be used for direct semi-quantitative analysis.

Laser ablation and ionization in ambient helium and argon gases were studied by multiple-stage time-of-flight mass spectrometry. Measurements made at different gas pressures indicated that there exists an optimal pressure for adequately cooling energetic ions and reducing multiply charged ions that are higher for He than for Ar. The temporal distributions of ions were compared at various laser fluences and gas pressures, and the broad distributions for He could be ascribed to elastic scattering and thermodynamic processes. The diffusion of ions in He resulted in a longer delay before the instrument registered its maximal signal. Ions with different masses were observed to have the same kinetic energies in He, which was confirmed using the SIMION software, while ion movement was hydrodynamically controlled in Ar. The velocities of singly and doubly charged ions were also studied, and doubly charged ions showed much higher kinetic energy because of their frontal location in the plasma expansion.

Influence of laser wavelength, laser irradiance and the buffer gas pressure were studied in high irradiance laser ablation and ionization source coupled with an orthogonal time-of-flight mass spectrometer. Collisional cooling effects of energetic plasma ions were proved to vary significantly with the elemental mass number. Effective dissociation of interferential polyatomic ions in the ion source, resulting from collision and from high laser irradiance, was verified. Investigation of relative sensitivity coefficients (RSC) of different elements performed on a steel standard GBW01396, which was ablated at 1064 nm, 532 nm, 355 nm, and 266 nm, has demonstrated that the thermal ablation mechanism could play a critical role with the first three wavelengths, while 266 nm induces non-thermal ablation principally. Experimental results also indicated that there is no evident discrepancy for most metal elements on RSCs and LODs among four wavelengths at high irradiance, except that high boiling point elements like Nb, Mo, and W have higher RSCs at higher irradiance regions of 1064 nm, 532 nm, and 355 nm due to thermal ablation. A geological standard and a garnet stone were also used in the experiment subsequently, and their RSCs and LODs for metal elements show nonsignificant dependence on wavelength at designated irradiances. All results reveal that relatively uniform sensitivity can be achieved at any wavelength for metal elements in the solids used in our experiments at an appropriate irradiance for the low pressure high irradiance laser ablation and ionization source.

Semiquantitative multielemental analyses of biological samples (tea leaf standard, Laminaria japonica, and pig skin) were demonstrated with a newly developed laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS). The sample was directly ablated and ionized with high irradiance after simple sample preparation. Relative sensitivity coefficients (RSC) were calculated and evaluated for sensitivity differences. Due to the employment of a collisional cooling device and the orthogonal geometry of the TOF system, high resolving power can be obtained, such that elemental peaks and interferential peaks with the same nominal mass can be distinguished. The detection limit of µg g−1 levels can be commonly achieved for elemental determination.

A novel laser ablation and ionization time-of-flight mass spectrometer has been used for direct elemental analysis of alloys. The system was incorporated with an ion guide cooling cell to reduce the kinetic energy distribution for the purpose of better resolution. Parametric studies have been conducted on the system with respect to the buffer gas pressure and the distance from sample to the nozzle to obtain the maximal signal intensities. In order to obtain satisfactory relative sensitivity coefficients (RSC) for different elements, the influence of the laser irradiance, nozzle voltage, rf frequency and voltage of the hexapole were also investigated. Under the optimized conditions, the RSC of different elements were available for direct semi-quantitative analysis. The mass resolving power (FWHM) of the spectrometer was approximately 7000 (m/Δm) and the limit of detection (LOD) was 10− 6 g/g.

A system was proposed to remove the upper mass limitation of mass spectrometry. In present study, ultra large molecules were separated in the gas phase by mass analyzer after electrospray ionization. Instead of conventional detection with electron multiplier, a laser-induced-fluorescence detection scheme was applied. The instrument sensitivity is independent of molecular weight, but related to the spectroscopic properties of the fluorophores presented by the large biomolecules.

Semiquantitative multielemental analyses of biological samples (tea leaf standard, Laminaria japonica, and pig skin) were demonstrated with a newly developed laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS). The sample was directly ablated and ionized with high irradiance after simple sample preparation. Relative sensitivity coefficients (RSC) were calculated and evaluated for sensitivity differences. Due to the employment of a collisional cooling device and the orthogonal geometry of the TOF system, high resolving power can be obtained, such that elemental peaks and interferential peaks with the same nominal mass can be distinguished. The detection limit of μg g−1 levels can be commonly achieved for elemental determination.Semiquantitative multielemental analyses of biological samples were demonstrated with a newly developed laser ionization orthogonal time-of-flight mass spectrometer (LI-O-TOFMS). Little sample preparation, few spectral interferences, high resolving power, and μg g−1 LOD were achieved.Download high-res image (101KB)Download full-size image

A method has been developed that allows the direct measurement of the elemental composition of geological samples based on a newly developed laser plasma time-of-flight mass spectrometer with a collisional cooling system. This technique has the merits of small sample consumption and rapid elemental analysis. Four geological reference materials were used in the experiment. The system has shown a satisfactory resolving power with few interferences in the spectra. The limits of detection were about 10−6–10−7 g g−1 for most of the metal elements. The relative sensitivity coefficients (RSCs) of the elements with mass heavier than 30 amu could be used for direct semi-quantitative analysis.

A laser ionization orthogonal time-of-flight mass spectrometer with a low-pressure source and high laser irradiance was used to analyze 27 solid samples with 9 different matrices, including aluminium, soil, copper sulfide, zinc sulfide, iron, nickel, copper, zinc, and tungsten. The influence of laser energy on non-stoichiometric effects, such as matrix effects and elemental fractionation, has been investigated. The results indicate that matrix effects can be alleviated to a great extent at high laser irradiance. Additionally, with the irradiance of 1010–1011 W cm−2, most elements presented relatively stable relative sensitivity coefficients (RSC), while W, Pb, and Bi demonstrated unusual characteristics that their RSCs increased along with increasing laser energy.

A novel strategy for the generation of metal–peptide complexes in the gas phase is proposed, which is of great value for probing the interactions of “naked” metal ions with peptides. “Naked” metal ions are generated from the metal target by laser ionization (LI) in open air, whereas gas-phase peptide ions are electrosprayed separately, facilitating the formation of gas-phase metal–peptide complexes. Compared to the conventional electrospray ionization (ESI) method, more control is offered for generating complexes, avoiding signal suppression and dilution effects induced by electrospraying solutions composed of metal salts and peptides. Higher stabilities of metal–peptide complexes can be obtained by a direct gas-phase reaction of peptides with “naked” metal ions devoid of counter-ions and surrounding solvent due to stronger noncovalent interactions, such as coulomb interactions and charge–dipole interactions. This approach leads a knowledge of the intrinsic properties of complexes and provides accurate gas-phase results in closer proximity to theoretical calculations irrespective of the solvent effect. The influence of the number and position of basic residues in peptides on the binding site of metal ions and CID fragmentation patterns of complexes is explored and discussed. Plausible mechanisms responsible for fragments remote from the initial binding sites of metal ions are proposed. Additionally, the diffusion model is introduced to expound on the high reaction yield of metal–peptide complexes and distribution evolution of metal ions, verified by both the calculated and experimental results.

High irradiance femtosecond laser ionization orthogonal time-of-flight mass spectrometry (fs-LI-O-TOFMS) has been applied for the depth profile analysis of multilayer samples. Elements in each layer can be determined with respect to the depth of solid sample surfaces. A nanosecond laser was also applied in parallel for comparison. The analytical performances as well as crater formation mechanisms of femtosecond and nanosecond laser ablation and ionization were compared. Superiorities of the depth resolution and trace elemental detection were observed in the femtosecond laser mode. fs-LI-O-TOFMS is capable of presenting the complete and explicit spectrum for each laser shot, performing depth profiling of coated layers with various thicknesses (tens of nanometers to tens of micrometers), providing multi-elemental information, and examining samples with conductive and nonconductive substrates.

This review focuses on the developments of atomic spectrometry (AS) in China since the founding of the People's Republic in 1949. The content covers atomic emission spectrometry (AES), atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS), and elemental mass spectrometry (ElemMS), together with related hyphenated techniques and sample introduction techniques. The first section covers the topic of the development history of atomic spectrometry in China. The intriguing developments in instrumentation, technique and methodology are listed with novel excitation/atomization sources highlighted. The second section deals with the aspects of hyphenated techniques, including on-line sample pre-treatment method for separation/preconcentration, and the chromatography-atomic spectrometry hyphenated techniques. The third section briefly demonstrates sample introduction techniques, which are vital for the enhancement of detectability. All these works indicate that the advancement of AS in China contributes to the development of methodology, application and instrumentation in the AS world.

A graphical abstract is available for this content

The utilization of laser sampling technique in analytical spectrometry has long prevailed as it does not require sample pretreatment, large samples or cause contamination. However, it suffers from a series of defects such as elemental fractionation, matrix effect and shortage of matrix-matched reference materials for most samples of interest. To correct these undesired effects and achieve better analytical performance, it is vital to be conscious of when and how the above deflecting effects occur, to what extent the various parameters involved influence them, and what means can be applied to minimize them. The present review summarizes the research work dealing with elemental fractionation and matrix effects in laser sampling approaches. The review is arranged as follows: Various phenomena of these effects in laser sampling based spectrometry are presented in Section 2; the processes involved are discussed in Section 3; subsequently, the impact of laser parameters and ablation background gas is discussed in Section 4 and 5, respectively; several theoretical studies concerning element-/matrix-specific ablation behavior are briefly considered in Section 6; the means to ultimately minimize elemental fractionation and matrix effect are presented in Section 7; and artificial matrix matched/non-matrix matched analysis approaches are summarized in Section 8.

Peptidomics plays an important role in clinical proteomics and disease-associated biomarker discovery. It has exhibited mounting potential in early noninvasive diagnosis, prognosis, and treatment evaluation of diseases. This article presents an introduction of peptidomics, the entire peptidomic workflows for serum and urine samples, and a brief overview of recent works in this area. The review is designed to enable researchers to find the most suited strategy for their peptidome studies.

An elemental analysis method was established to monitor the element levels in serum samples of 38 healthy controls and 38 stone patients. Based on the optimized platform combined with multivariate analysis, satisfactory results can be obtained for urinary lithiasis diagnosis with the concentrations of 9 elements, in which Ba, Ga, Sb, and Na are the top 4 elements of statistical significance. The patients could be subdivided into calcareous and non-calcareous stone patients by metallomic profiling; and it is found that Se plays the major role in this classification. This study indicates that serum elementary analysis gives an insight into the possibility of diagnosis of urinary lithiasis, subsequently it may allow estimation of the content subtype of stones. By means of this simple method of elemental profiling in serum, it might allow early prognosis and treatment guide to urinary lithiasis.

High-irradiance laser ionization time-of-flight mass spectrometry (LI-TOFMS), an established technique for elemental determination, has been applied for the analysis of metalloporphyrins. Many porphyrins and their metal complexes, being organometallic compounds, are hard to dissolve in general organic solvents, hampering the wider application of traditional mass spectrometric techniques. With LI-TOFMS, an environmentally friendly analytical strategy has been demonstrated, which is capable of matrix- and solvent-free analysis of metalloporphyrins, with advantages including direct solid sampling, ease of implementation, and avoidance of sample pre-treatment. Moreover, information about elemental composition, fragments, and intact molecules can be obtained simultaneously using LI-TOFMS, hence expediting the identification of metalloporphyrins. A comparative study of LI-, laser desorption ionization (LDI-), matrix-assisted laser desorption ionization (MALDI-) and electrospray ionization (ESI-) mass spectrometry (MS) has also been conducted.

Characteristics of laser ionization in vacuum and low pressure background gas (He) have been investigated through the measurement of kinetic energy and spatial distributions of copper and tungsten ions. A Q-switched Nd:YAG laser with 532 nm wavelength was utilized and the laser irradiance was fixed at 9 × 109 W cm−2. A plume splitting was observed in the low pressure regime investigated (from 100 Pa to 2000 Pa). The plume propagation translates from a free expansion in vacuum to shockwave-like expansion at relative low pressure and finally diffusion into background gas at relative high pressure environment. A measurement of ion spatial distribution in the ion source has also been carried out for characterizing ions at different pressures and the behaviors of doubly charged, singly charged, and polyatomic ions to reveal the effect of plume–background gas interaction.